The paranasal sinuses require adequate ventilation to prevent microbial chronic infection within the sinus cavities. Normally, ventilation is provided through the small natural openings, known as ostia, through which the sinus cavities open into the nose. In addition to ventilation, the natural ostia serve as drainage channels as ciliated cells lining the interior of the sinus cavity continually direct a flow of mucus toward the ostia. Thus, when the natural ostia become narrowed or blocked, ventilation and drainage from the sinus cavity is impaired. The resultant hypoxia, pH changes and mucus stasis within the sinus cavity gives rise to an environment in which some types of microbial growth can flourish. Such microbial infection can, in itself, result in further mucosal inflammation and even further constriction or blockage of the natural sinus ostium.
Techniques for Improving Ventilation and Drainage of Paranasal Sinuses
Functional endoscopic sinus surgery (FESS) is a common type of surgery wherein an endoscope is inserted into the nose and, under visualization through the endoscope, the surgeon may remove diseased or hypertrophic tissue or bone and may surgically enlarge the ostia of the sinuses to restore normal ventilation and drainage of the sinuses.
As an alternative to incisional surgery, in some patients, a balloon catheter may be advanced into the constricted sinus ostium and used to dilate the ostium, thereby eliminating the need for cutting or removing tissue surrounding the ostium (Balloon Sinuplasty™ technology, Acclarent, Inc., Menlo Park, Calif.). Examples of such balloon dilation procedures are described in United States Patent Application Publications No. 2006/0004286, 2006/0063973, 2006/0210605, 2007/0129751, 2007/0135789, 200710167682, 2007/0208252, 2007/0208301 and 2007/0293727, the entire disclosure of each such patent application being expressly incorporated herein by reference.
Implantation of Stents and Space Occupying Materials to Deter Re-Occlusion Following Surgery
In cases where tissue adjacent to the ostium has been surgically removed or incised, post-operative scar tissue, fibrosis, polyposis or tissue ingrowth can result in re-occlusion of the sinus ostium. To deter such re-occlusion of frontal and sphenoid sinuses following surgery, small tubular stents have been placed in the surgically altered sinus ostium or outflow tract for a limited time period following surgery.
One example of a commercially available frontal sinus stent is the Freeman™ Frontal Sinus Stent (InHealth Technologies, Inc., Carpinteria, Calif. The Freeman™ stent comprises a silicon tube that has flanges on either end to retain the stent within the frontal outflow tract for a desired period of time following surgery. Other commercially available frontal sinus stents include the Jasin Frontal Sinus Stent (Medtronic Xomed, Inc., Jacksonville, Fla.), and the Salman FES Stent (Boston Medical Products, Westborough, Mass.).
A sphenoid sinus stent is described in U.S. Pat. No. 7,235,099 (Duncavage, et al.). This stent comprises a soft compressible plastic tube having a generally hemispherical hollow dome on one end. The diameter of the dome is greater than the predetermined diameter of the plastic tube. The stent further includes an annular flange located a predetermined distance from the hemispherical dome. The device is designed to be fitted through a surgically enlarged ostium of the sphenoid sinus such that the dome resides within the sinus cavity and the flange abuts the bony wall surrounding the ostium. This stent serves maintain patency of the surgically altered ostium during the postoperative period and allows irrigation/suctioning through the lumen of the stent. This sphenoid sinus stent is also commercially available as the SP-82020 Sphenoid Sinus Stent (Micromedics, Inc., St. Paul, Minn.).
The above-described frontal and sphenoid sinus stents do not deliver therapeutic substances. Thus, they are frequently used concurrently with orally administered drugs (e.g., corticosteroids) and/or topical nasal sprays.
In some cases, in lieu of a stent, surgeons may place gel-like materials within the surgically altered ostium or outflow tract to prevent ingrowth of scar tissue during the post-surgical period. One example of such material is the MeroPack™ Bioresorbable Nasal Dressing and Sinus Stent available from Medtronic ENT, Inc., Jacksonville, Fla. The MeroPack™ material consists of 80 percent esterified hyaluronic acid and 20 percent collagen. This material is inserted while in its dry state and, upon hydration, swells to 1.0 cm diameter in about six seconds. When in its hydrated state, this material is a biocompatible, muco-adhesive gel.
Local Drug Delivery in the Treatment of Sinus Disease
Various drug delivery implants have been proposed for use in or around the paranasal sinuses to treat sinusitis and/or to deter re-occlusion of surgically altered outflow tracts or ostia following surgery.
For example, United States Patent Application Publication No. 20050043706 (Eaton et al.) describes biodegradable implants for treating sinusitis, such implants having a size, shape, density, viscosity, and/or mucoadhesiveness that prevents them from being substantially cleared by the mucociliary lining of the sinuses during the intended treatment period. These biodegradable implants deliver therapeutic agents such as antibiotics, steroids or both. These biodegradable implants may be in various forms such as rods, pellets, beads, strips, or microparticles, and may be delivered into a sinus in various pharmaceutically acceptable carriers.
Also, United States Patent Application Publication No. 20070005094 (Eaton et al.) describes implantable devices useable for the treatment of paranasal sinus conditions. The devices include cavity members that have a first collapsed configuration that permits the device to pass through a sinus ostium and a second expanded configuration after placement into the sinus cavity. In addition to a cavity member, the devices may include a nasal portion and an ostial member that is configured to reside within the sinus ostium. The cavity member is attached to the distal end of the ostial member. The nasal portion is attached to the proximal end of the ostial member and lies within the nasal passage. The active agent may be incorporated into all portions of the device or only included in the expandable cavity member, the ostial member, or nasal portion.
Some investigators have proposed adding drug delivery capability to frontal sinus stents to deliver controlled amounts of drug to the surgically altered outflow tract following frontal sinus surgery. For example, United States Patent Application Publication 2004/0116958A1 (Gopferich et al.) describes a tubular sheath or “spacer” formed of biodegradable or non-biodegradable polymer that, prior to insertion in the frontal outflow tract, is loaded with a controlled amount of an active substance, such as a corticosteroid or anti-proliferative agent. After surgery to create a fenestration in a frontal sinus as been performed, the sheath (which has been preloaded with the active substance) is inserted into the surgically created fenestration where it a) deters closure of the surgically created fenestration, b) serves as a conduit to facilitate drainage from the sinus and c) delivers the active substance. In some embodiments, the sheath is formed of multiple layers of polymeric material, one or more of which is/are loaded with the active substance and one or more of which is/are free of the active substance. In other embodiments, the sheath has a “hollow body” which forms a reservoir system wherein the active substance is contained and a membrane which controls the release of the active substance from the reservoir. In some embodiments, the sheath may be anchored by causing the end of the sheath that extends into the sinus to swell or otherwise enlarge. Also, United States Patent Application Publication No. 2005/0245906 (Makower et al.) describes a biodegradable polymeric device that comprises a spacer positionable within a sinus ostium. The spacer has a plurality of substance-eluting struts. The device may be implanted such that the struts are substantially parallel to the cilial flow of mucus along the sinus cavity walls so that normal mucociliary transport is not interrupted.
Additionally, various other types of implantable drug delivery devices have been proposed for use in the nose and/or paranasal sinuses. For example, U.S. Pat. No. 3,948,254 (Zaffaroni) describes implantable drug delivery reservoirs having microporous walls. The reservoir may be formed of a solid drug carrier that is permeable to passage of the drug and the rate of passage of the drug through the microporous wall may be slower than the rate at which the drug passes through the solid drug carrier that forms the reservoir. Zaffaroni also describes a number of applications for the implantable drug delivery devices including placement in a nasal passage. Specifically, Zaffaroni claims a nasal delivery device for dispensing a drug within a nasal passage at a controlled rate wherein the nasal device is comprised of (a) a wall defining the device dimensioned for insertion and placement within a nasal passage, with the wall formed of a nasal acceptable microporous material, (b) a reservoir surrounded by the wall and comprised of a solid carrier permeable to drug and containing drug in an amount sufficient for the device to meter it at a continuous and controlled rate for a prolonged period of time from the device, (c) a liquid medium permeable to the passage of drug by diffusion charged in the micropores, and (d) wherein the device releases drug when in a nasal environment by passage of drug from the carrier and through the liquid to the exterior of the device to produce a useful result. The entire disclosure of U.S. Pat. No. 3,948,254 (Zaffaroni) is expressly incorporated herein by reference.
Other publications have also reported that introduction of drugs directly into the paranasal sinuses is effective in the treatment of sinusitis. See, Tarasov, D. I., et al., Application of Drugs Based on Polymers in the Treatment of Acute and Chronic Maxillary Sinusitis, Vestn Otorinolaringol. Vol. 6, Pages 45-7 (1978). Also, R. Deutschmann, et al., A Contribution to the Topical Treatment of [Maxillary] Sinusitis Preliminary Communication, Stomat. DDR 26 (1976), 585-592 describes the placement of a resorbable drug delivery depot within the maxillary sinus for the purposes of eluting drugs, specifically Chloramphenicol. In this clinical series a water soluble gelatin was used as carrier and was mixed with the drug prior to application and introduced as a mass into the sinus. Since the substance had little mechanical integrity and dissolved in a relatively short timeframe, to achieve a therapeutic effect, the author suggested that it must be instilled every 2 to 3 days. An alternative to gelatin could be a sponge loaded with the therapeutic substance as suggested in U.S. Pat. No. 6,398,758 (Jacobsen, et al.). In this patent directed at delivering a sustained release device against the wall of a blood vessel, a hollow cylindrical sponge is loaded with drug and pressed against the wall. This allows the drug to contact the wall while sustaining blood flow within the center of the lumen. Further, a skin is provided to direct the drug into the walls of the blood vessel and prevent drug from flowing into the lumen. While sponges loaded with drug at the time of their application do permit some degree of sustained release, the time required to load them also correlates closely the time over which they will elute substance. Thus, if delivery is required for a longer period of time additional mechanisms must be employed to regulate their release.
There are also several examples in the patent literature where various sustained release mechanisms have generally been proposed using systems with drugs pre-incorporated into matrices or polymers. These include U.S. Pat. No. 3,948,254 (Zaffaroni), US 2003/0185872A2 (Kochinke), WO 92/15286 (Shikani), and U.S. Pat. No. 5,512,055 (Domb, et al.). In general, these references discuss various materials and structures that may be used to construct sustained drug delivery vehicles and provide a good overview of the state of sustained drug delivery art. While helpful in laying out certain materials and schemes for creating sustained release systems for drugs, these references do not, however, describe specific methods, means or structures which would permit them to be easily adapted for intended uses that are targeted in the present application.
Other examples of implantable drug delivery devices include those described in U.S. Pat. Nos. 3,993,073; 4,217,898; 5,304,123; 6,042,561; 6,183,461; 6,780,168 and 6,783,522, the entire disclosure of each such patent being expressly incorporated herein by reference.
Techniques for Treatment of Ethmoid Disease
To date, the use of stents and spacers in relation to nose and sinus surgery has been largely limited to placement in the frontal outflow tract or sphenoid sinus ostium following surgery wherein tissue and bone have been cut away or removed. However, as new devices and methods become available for the treatment of other types of nasal and sinus disorders, there will likely be a need for intranasal or sinus spacers and stents (with or without drug eluting capabilities) suitable for placement at various locations lot limited to the frontal outflow tract.
In the prior art, diseased ethmoid air cells have sometimes been treated by a procedure known as an ethmoidectomy wherein a man made passageway is formed between the interiors of the ethmoid air cells and the nasal cavity. Stenting and/or delivery of drugs or other therapeutic substances into these manmade ethmoidectomy passageways has been, in at least some cases, desirable. To accomplish this, strips of gauze soaked with medication may be pushed into the manmade opening and later extracted. Also, in this regard, U.S. Pat. No. 6,543,452 (Lavigne) describes a nasal intubation device that comprises a flexible tube having a flanged distal tip whereon the flanges generally from an arrow shape. The distal tip of this device is capable of penetrating through tissue (e.g., through the ethmoid bulla) to a desired position (e.g., within the ethmoid air cells). Openings are formed in a distal portion of the intubation device so that medication (e.g., a typical steroid) injected through the flexible tube will flow out of the tube into contact with the adjacent area (e.g., the diseased ethmoid air cells). In some cases, a cannula-trocar may be initially inserted and the nasal intubation device may then be advanced through that cannula-trocar. Also, European Patent Publication EP0624349 (Milewski) describes a balloon-tipped catheter having an anatomically shaped balloon which may be inserted through a surgically created opening into a body cavity (e.g., frontal sinus or ethmoid cell) and inflated to create a tamponade by being shaped to suit the anatomical shape of the cavity.
There remains a need in the art for the development of new devices and methods for delivering drugs and other therapeutic or diagnostic substances over a sustained period of time into paranasal sinuses, Eustachian tubes, middle ear and/or other locations within the body for the treatment of sinusitis, otitis or other diseases and disorders.